Sigma ligands for neuronal regeneration and functional recovery

Abstract

The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably AGY-94806, or salts, or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by multiple sclerosis. In other methods, the sigma receptor ligands are administered after MS to facilitate functional recovery. The administration of the sigma receptor ligands causes faster functional recovery.

1. A method of treating multiple sclerosis in a mammalian subject, the method comprising administering to the subject an effective amount of 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine, or a pharmaceutically acceptable salts thereof, after onset of multiple sclerosis to facilitate functional recovery and thereby decrease the symptoms and progression of multiple sclerosis. 
     
     
       2. The method as claimed in  claim 1 , wherein the salt is a salt formed with hydrochloric acid. 
     
     
       3. The method as claimed in  claim 1 , wherein the effective amount is in the range of about 1 mg to about 300 mg. 
     
     
       4. The method as claimed in  claim 1 , wherein the functional recovery is recovery in a motor skill, cognitive skill, speech, sensory perception or sensory function. 
     
     
       5. The method as claimed in  claim 4 , wherein the functional recovery is recovery in a motor skill. 
     
     
       6. The method as claimed in  claim 4 , wherein the functional recovery is recovery in a cognitive skill. 
     
     
       7. The method as claimed in  claim 1 , wherein the sigma ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine, or a pharmaceutically acceptable salt thereof, is administered repeatedly to the subject until evidence of functional recovery is found. 
     
     
       8. The method as claimed in  claim 7 , wherein the sigma ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine, or a pharmaceutically acceptable salt thereof, is administered daily. 
     
     
       9. The method as claimed in  claim 1 , wherein the mammalian subject is a human. 
     
     
       10. The method of  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered for at least 2 weeks. 
     
     
       11. The method of  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered for 1 month. 
     
     
       12. The method of  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered for 3 months. 
     
     
       13. The method of  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered for 3 months or longer. 
     
     
       14. The method of  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered continuously. 
     
     
       15. The method as claimed in  claim 1 , wherein 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine is administered repeatedly to the subject until evidence of functional recovery is found. 
     
     
       16. The method as claimed in  claim 1 , wherein the mammalian subject is a human.